ECOTOX: A Foundation for Extrapolation

Transcription

1 ECOTOX: A Foundation for Extrapolation Christine Russom U.S. EPA/ORD/NHEERL/MED Presented at the McKim Conference on the Use of QSARs June 27-29, 29, 26 What is ECOTOX? ECOTOX is a comprehensive web-based database of effects of single chemicals to aquatic and terrestrial organisms Developed and maintained by U.S. EPA Primary source of data are the studies published in the open literature Information regarding study design and test results are presented in discrete data fields 1

2 Evaluating Ability of ASTER Toxicity Models to Predict Independent Test Results 2 Predicted log LC5 (moles/l) Observed log LC5 (moles/l) 2

3 1 Brook Trout: Total PCB (ug/g) Total PCB (ug/g ww) Adults: NOEL Adults: LOEL Juveniles: NOEL Juveniles: LOEL Eggs/Embryos: NOEL Eggs/Embryos: LOEL Biochemical Physiology Reproduction Growth Mortality Population Data Requirements Paper is the primary source of the data Observed effect / no effect responses resulting from a chemical exposure Species and chemical information must be verifiable Single chemical exposures Reports chemical concentration, dose, or application rate Duration of exposure provided Exposure must be to an intact, live organism Sediment studies must include a pore water concentration Database does not include bacteria, viral, and yeast studies Database does not include petroleum (fuel oils) products Database does not include inhalation studies 3

4 ECOTOX Procedures Develop Literature Search Strategy QA - Verify terms used; test strategy; etc. Conduct Literature Search QA - Assess effectiveness of search; validate exclusion terms; etc. Identify and Acquire Potentially Applicable Literature QA Maintain database of all papers acquired; verify papers identified as nonapplicable; etc. Codify / Abstract Relevant Data QA Training procedure; 1% replicate review; electronic checks; verification of species/chemical information; data entry QA; etc. Release of New Data to Public Website QA Code verification; Agency IT requirements; beta-testing prior to public release; etc. Outreach / Technical Support QA User support line; data maintenance; web-site documentation / help file; etc. ECOTOX What is encoded All pertinent data presented by the authors is abstracted from published literature and encoded into the database Species Chemical Test Methods Tests Results Source of information 4

5 ECOTOX What is encoded Information Coded for Test Organism Common name Scientific name Taxonomic hierarchy Sex Age Initial weight and length Initial life stage Comments on organism noted by author ECOTOX What is encoded Information Coded for Test Compound CAS Registry number Collective indices name Synonyms Chemical form Chemical purity Solvent / vehicle used Chemical class / group 5

6 ECOTOX What is encoded Test Methods Route of exposure Exposure media Duration of study and/or exposure Application frequency Date and geographic location of field studies Location of study (field vs. laboratory) Water chemistry and physical characteristics of test media Comments on experimental design Control type Whether chemical concentrations are measured vs. nominal ECOTOX What is encoded Tests Results Observed effect measurements (e.g., P45 enzyme measurements Major effect category (e.g., Enzyme) Any calculated (e.g., BCF) or statistically derived endpoint (e.g., LD5, NOAEL, LOAEL) If the authors do not clearly state the endpoint, but one can be inferred from a statistical presentation of the data (Table or Figure), then the appropriate endpoint is encoded with a flag that the endpoint was assigned by the reviewer Statistical information related to the endpoint is captured including the level of significance Responses observed at each dose for terrestrial studies 6

7 ECOTOX Effects Observed Effect Responses Accumulation Behavior (e.g., avoidance and feeding behavior) Biochemical, enzyme and hormonal responses Growth, development and morphological changes Cellular, genetic and histological responses Mortality Physiological changes, injury, immunity, and intoxication Population Effects Reproduction Ecosystem Response 7

8 Data Mining Can conduct searches on any coded parameters Search on recent updates to the database Taxonomy, common or scientific name, plant vs. animal Independently compiled data sets CAS Registry No., chemical name, chemical group Endpoints (e.g., LC5); effect groups (e.g., mortality, growth); measurement (e.g., time to death, weight) Test conditions: study location (lab vs. field); test media (e.g., freshwater, soil); route of exposure (e.g., diet); chemical analysis (measured vs. nominal) Publication information: ECOTOX reference number; specific publication years; range of publication years ECOTOX Linkages ECOTOX Chemical Database Species Database Toxic Effects Database (AQUIRE; PHYTOTOX; TERRETOX) Reference Database ASTER System Expert system Evaluated Data : (PCB Effect/Residue data; Toxicity Reference Values; Superfund/Eco-Soil Screening Levels, Endangered species assessments; Water Quality Criteria data) Third-party Data Sources (e.g., OECD, USGS, EPA) 8

9 N u m b e r o f T e s t R e s u lt s B i r d s M a m m a l s F i s h 8 6 Percentage of data by endpoint type 4 2 L C 5 L D 5 L O E L / L O E C N O E L / N O E C B A F / B C F L T 5 E C 5 M A T C R a i n b o w t r o u t F a t h e a d m i n n o w B l u e g i l l C o m m o n c a r p C h a n n e l c a t f i s h G o l d f i s h G u p p y M e d a k a S h e e p s h e a d m i n n o w Z e b r a f i s h C o h o s a l m o n M o s q u i t o f i s h B r o o k t r o u t S t r i p e d b a s s T i l a p i a C a r p A t l a n t i c s a l m o n C u t t h r o a t t r o u t C h i n o o k s a l m o n L a r e g e m o u t h b a s s 1 5 Fish data in ECOTOX with Endpoints reported Top 2 species 1 5 N u m b e r o f E n d p o i n t r e s u l t s b y S p e c i e s 9

10 N o r w a y r a t H o u s e m o u s e D e e r m o u s e M i n k G e r b i l W h i t e - f o o t e d m o u s e D o g E u r o p e a n r a b b i t P i g A n t e l o p e 1 Mammalian data in ECOTOX with Endpoints reported Top 1 species N u m b e r o f E n d p o i n t r e s u l t s b y S p e c i e s M a l l a r d B o b w h i t e J a p a n e s e q u a i l R i n g - n e c k e d p h e a s a n t B a n t a m c h i c k e n E u r o p e a n s t a r l i n g H o u s e s p a r r o w C o m m o n g r a c k l e R o c k d o v e R e d - w i n g e d b l a c k b i r d A m e r i c a n k e s t r a l C h u k a r p a r t r i d g e H e l m e t e d g u i n e a f o w l G r a y p a r t r i d g e B r o w n - h e a d e d c o w b i r d A m e r i c a n b l a c k d u c k M o u r n i n g d o v e R e d - l e g g e d p a r t r i d g e Q u a i l H e r r i n g g u l l 1 Avian data in ECOTOX with Endpoints reported Top 2 species N u m b e r o f E n d p o i n t R e s u l t s b y S p e c i e s 1

11 C o p p e r s u lf a t e A m m o n iu m c h lo r id e Z in c s u lf a t e F e n it r o t h io n T h io s u lf a n Z in c c h lo r id e M a la t h io n E n d r in T r ic h lo r o f o n M e r c u r y c h lo r id e C a d m iu m c h lo r id e P e n t a c h lo r o p h e n o l 3 - T r if lu o r o m e t h y l- 4 - n it r o p h e n o l P o t a s s iu m d ic h r o m a t e C a r b a r y l P h e n o l L in d a n e R o t e n o n e D ia z in o n T o x a p h e n e 2 Fish data in ECOTOX with Endpoints reported Top 2 Chemicals N u m b e r o f E n d p o i n t R e s u l t s b y C h e m i c a l A r o c h lo r D ie ld r in C a r b a r y l D io x in M ir e x L e a d a c e t a t e K e p o n e N it r o f e n T r ic lo r o f o n T h io p h a n a t e - m e t h y l 1 8 Mammalian data in ECOTOX with Endpoints reported Top 1 Chemicals N u m b e r o f T e s t R e s u l t s b y C h e m i c a l 11

12 D ie ld r in F e n t h io n D ia z in o n P a r a t h io n S t r y c h n in e D D T K e p o n e M e r c a p t o d im e t h u r M e t h y lm e r c u r ic d ic y a n d ia m id e A r o c h lo r D ic r o t o p h o s M e r c u r y b ic h lo r id e E n d r in T e m e p h o s C a r b o f u r a n P a r a q u a t d ic h lo r id e C a r b a r y l 1 - N a p h t h y lt h io u r e a C h lo r p y r if o s p, p '- D D E Avian data in ECOTOX with Endpoints reported Top 25 Chemicals N u m b e r o f T e s t R e s u l t s b y C h e m i c a l N o n p o la r n a r c o s is P o la r n a r c o s is A C h E in h ib it io n N e u r o t o x ic a n t R e a c t iv e E s t e r n a r c o s is U n c o u p le r o f o x id a t iv e p h o s p h o r y la t io n R e s p ir a t o r y b lo c k e r 6 5 MOA for Organic Chemicals in ECOTOX with concurrent structure information P e r c e n t a g e o f C h e m i c a l s b y M O A 12

13 Summary of Data in ECOTOX Fish, mammals and birds Total Number of Test results in ECOTOX: 52,622 No. of test results for fish: 111,726 (65% have Endpoints) No. of test results for mammals: 89,47 (2% have Endpoints) No. of test results for birds: 36,17 (12% have Endpoints) Total Number of Chemicals in ECOTOX: 1,372 No. of unique chemicals in fish subset: 5,372 No. of unique chemicals in mammal subset: 743 No. of unique chemicals in bird subset: 752 Total Number of Species in ECOTOX: 6,137 No. of unique fish species: 731 No. of unique mammal species: 87 No. of unique bird species: 13 Total number of publications in ECOTOX: 19,551 No. of papers associated with fish data: 7,876 No. of papers associated with mammalian data: 652 No. of papers associated with bird data: 424 Anne Pilli (CSC) Delores Grunwald (CSC) Brian Kinziger (CSC) Amy Puglisi (CSC) Steve Erickson (CSC) Joanne Kobus (CSC) Dan Peterson (CSC) Greg Elonen (CSC) Sue Tranmel (CSC) Brian Ness (CSC) Kraig Hessen (CSC) Wendy Hieb (CSC) Christina Wagner (CSC) Jason Selin (CSC) Anita Pompulin (CSC) Tom Berrisford (CSC) David Burress (CSC) James Niesen (CSC) Sandra Purcell (CSC) Gina Skopinski (CSC) Matt Abel (CSC) Amanda Paul (CSC) Susan Rees (CSC) Pamela Baker (CSC) Donna Swenson (CSC) Gil Veith (formerly EPA) Rosemarie Russo (formerly EPA) Charles Stephan (EPA) Bob Spehar (EPA) Barb Sheedy (EPA) 13